Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration

• Published in: Journal of Allergy and Clinical Immunology 2005-04, Vol.115 (4), p.822-827
• Main Authors: Omata, Nemuko, Ohshima, Yusei, Yasutomi, Motoko, Yamada, Akiko, Karasuyama, Hajime, Mayumi, Mitsufumi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Allergic diseases; anergy; Animals; Biological and medical sciences; clonal deletion; Cytokines - analysis; Cytokines - immunology; Digestive allergic diseases; Female; Flow Cytometry; Food allergy; Fundamental and applied biological sciences. Psychology; Fundamental immunology; IgE; Immune Tolerance; Immunoglobulin E - immunology; Immunopathology; Medical sciences; Mice; Mice, Transgenic; oral tolerance; ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; T-Lymphocytes - immunology
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2004.12.1121

Some patients outgrow their food allergies even though their serum antigen-specific IgE levels remain high. To elucidate the role of T cells in outgrowing food allergies in the presence of antigen-specific IgE, we tracked antigen-specific T-cell responses after oral antigen administration. Ovalbumin (OVA)-specific T-cell receptor (TCR) and OVA-specific IgE transgenic (Tg) mice (OVA-TCR/IgE-Tg) and OVA-specific TCR Tg (OVA-TCR-Tg) mice were fed with high doses of OVA or PBS every other day. After 7 administrations, OVA-specific proliferation and cytokine production of mononuclear cells of the spleen, mesenteric lymph nodes, and Peyer's patches and the number of splenic CD4 +CD25 + T cells were analyzed. Without OVA administration, the splenocytes from OVA-TCR/IgE-Tg mice exhibited a higher proliferative response and produced more IL-4 and IL-10 and less IFN-γ than those from OVA-TCR-Tg mice. The proliferative responses of the splenocytes from either OVA-TCR/IgE-Tg mice or OVA-TCR-Tg mice fed with OVA were significantly reduced compared with those from PBS-fed mice. The number of OVA-specific TCR + T cells decreased in the spleen from OVA-fed mice, whereas the number of CD4 +CD25 + T cells increased. The suppressed proliferation of splenocytes of OVA-fed mice was partially resumed by neutralization of TGF-β1, but not of IL-10. The presence of OVA-specific IgE modulated the OVA-specific responses of the splenocytes. Irrespective of the presence of OVA-specific IgE, repetitive oral administration of OVA induced tolerance, which seems to be composed of clonal deletion/anergy and TGF-β1–mediated active suppression.